Is it safe to hypofractionate for whole breast RT in patients with a BRCA 1/2 or CHEK2 mutation to chose to have breast conservation for early stage breast cancer or DCIS?

There is no evidence that hypofractionation compared to conventional fractionation results in higher acute or long term toxicities in patients who have these mutations. Since a majority of these patients may also be in a younger age group many clinicians may appropriately feel uncomfortable in offering hypofractionation. So a conservative approach in offering standard fractionation to patients receiving radiation therapy who may be younger and have these mutations is of course quite reasonable and likely the approach a majority of clinicians will take. Having said that, I am not aware of any evidence that hypofractionation would not be safe for a BRCA1 or CHEK2 mutation carrier regardless of age. It is more a level of comfort on the part of...

I agree with @Dr. First Last about the lack of evidence of increased toxicity in patients with BRCA1/2 or CHEK2 alterations (or PALB2 etc) and frequently refer to his important work in this area. In START B there were 108 women <= 39 and 457 women <= 49 randomized. One of the most striking findings of the long-term follow-up published by Haviland et al. in 2013 was the significant reduction in breast shrinkage, telangiectasia, and breast edema and trend in reduction in breast induration with the hypofractionated arm investigated. Given the lack of data or strong radiobiological rationale for why patients with these genomic alterations may be at higher risk of toxicity (or have less reduction in toxicity with hypofractionation than the avera...